This study consists of 2 interrelated groups of projects. This first group of projects will provide a prototype for investigating whether antibody binding may permit a substance's access to the fetus whereas if it were present solely in the free form, it would be selectively inhibited from crossing the placental barrier. The transplacental transfer of the insulin-antibody complex will be the major focus of this project and, as such, will be fully characterized; other peptides or antigens may be studied relating to the concept of antibody as a carrier protein facilitating transplacental transfer. The second group of projects will relate to the transplacental passage of maternal insulin antibodies and its effects on the fetus; in particular, perturbations in free, presumably biologically active, fetal insulin with resultant functional and/or pathologic changes in the fetal pancreatic B-cell will be investigated. The methodology required to carry-out the project requires (1) standard insulin radioimmunoassay (RIA), (2) a sensitive species-specific RIA, (3) capacity to determine insulin concentration in insulin-treated patients or animals with insulin antibodies, (4) ability to measure insulin binding capacity, (5) standard cell separation and lymphocyte culture technique for 3H-thymidine incorporation, and (6) standard pathologic and immunohistochemical technique to determine pancreatic size and B-cell content. The concept of antibody as a carrier protein for transplacental transfer of noxious and/or beneficial substances to the fetus may have wide and varied clinical application. Questions of in utero immunologic tolerance and/or responsiveness may be applied to various disciplines, including endocrinology, immumology, pharmacology and infections diseases. Fetal hyperinsulinism has been known to be associated with characteristic developmental effects but the hypothesis that insulin antibodies are one cause of hyperinsulinism has not previously been addressed.